C2orf76

Summary

C2orf76 (chromosome 2 open reading frame 76, HGNC:27017) is a protein-coding gene on chromosome 2q14.2, encoding UPF0538 protein C2orf76 (Q3KRA6).

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_001322331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27017
Approved symbol	C2orf76
Name	chromosome 2 open reading frame 76
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC104437, LOC130355, AIM29
Ensembl gene	ENSG00000186132
Ensembl biotype	protein_coding
Entrez	130355

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000334816, ENST00000409466, ENST00000409523, ENST00000409877, ENST00000414534, ENST00000498049, ENST00000878326, ENST00000878327, ENST00000878328, ENST00000878329, ENST00000878330, ENST00000937463, ENST00000937464, ENST00000937465, ENST00000937466, ENST00000967572, ENST00000967573, ENST00000967574, ENST00000967575

RefSeq mRNA: 5 — MANE Select: NM_001322331 NM_001017927, NM_001322329, NM_001322330, NM_001322331, NM_001322332

CCDS: CCDS42739

Canonical transcript exons

ENST00000334816 — 6 exons

Exon	Start	End
ENSE00001335430	119311622	119311703
ENSE00001335434	119317466	119317503
ENSE00001335435	119321154	119321204
ENSE00001557732	119366790	119366834
ENSE00001578168	119302225	119302548
ENSE00003687102	119339827	119339971

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 90.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.3512 / max 61.8116, expressed in 1728 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30415	4.1582	1664
30414	1.0153	565
30416	0.1777	97

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	90.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.14	gold quality
calcaneal tendon	UBERON:0003701	89.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.86	gold quality
smooth muscle tissue	UBERON:0001135	87.89	gold quality
oocyte	CL:0000023	87.72	gold quality
spinal cord	UBERON:0002240	87.71	gold quality
secondary oocyte	CL:0000655	87.48	gold quality
monocyte	CL:0000576	87.40	gold quality
leukocyte	CL:0000738	87.14	gold quality
right adrenal gland	UBERON:0001233	87.05	gold quality
right adrenal gland cortex	UBERON:0035827	86.97	gold quality
left coronary artery	UBERON:0001626	86.53	gold quality
popliteal artery	UBERON:0002250	86.41	gold quality
tibial artery	UBERON:0007610	86.41	gold quality
left adrenal gland	UBERON:0001234	86.16	gold quality
left adrenal gland cortex	UBERON:0035825	86.16	gold quality
left uterine tube	UBERON:0001303	86.09	gold quality
pancreas	UBERON:0001264	85.79	gold quality
aorta	UBERON:0000947	85.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.49	gold quality
omental fat pad	UBERON:0010414	85.49	gold quality
right coronary artery	UBERON:0001625	85.44	gold quality
peritoneum	UBERON:0002358	85.42	gold quality
ascending aorta	UBERON:0001496	85.35	gold quality
thoracic aorta	UBERON:0001515	85.30	gold quality
amygdala	UBERON:0001876	85.23	gold quality
anterior cingulate cortex	UBERON:0009835	85.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting C2orf76, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-27B-5P	97.34	66.55	549

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C9H2orf76	ENSDARG00000037199
mus_musculus	3110009E18Rik	ENSMUSG00000026388
rattus_norvegicus	C13h2orf76	ENSRNOG00000045570

Protein

Protein identifiers

UPF0538 protein C2orf76 — Q3KRA6 (reviewed: Q3KRA6)

All UniProt accessions (2): C9JTA8, Q3KRA6

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the UPF0538 family.

RefSeq proteins (5): NP_001017927, NP_001309258, NP_001309259, NP_001309260, NP_001309261 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018794	UPF0538	Family

Pfam: PF10209

UniProt features (3 total): sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KRA6-F1	92.13	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WEI_MYCN_TARGETS_WITH_E_BOX, chr2q14, CHEN_LIVER_METABOLISM_QTL_CIS, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_36HR, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, CREB3L4_TARGET_GENES, FEV_TARGET_GENES, HES2_TARGET_GENES, KMT2D_TARGET_GENES, PRKDC_TARGET_GENES, RYBP_TARGET_GENES, SFMBT1_TARGET_GENES, ZFHX3_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf76	PLPBP	O94903	528
C2orf76	LTN1	O94822	467
C2orf76	COX14	Q96I36	418
C2orf76	GET3	O43681	412
C2orf76	CYP2A7	P20853	348
C2orf76	PBDC1	Q9BVG4	347
C2orf76	HGH1	P0CB43	344
C2orf76	GABRG3	Q99928	338
C2orf76	DBI	P07108	312
C2orf76	PAH	P00439	308
C2orf76	ST6GALNAC1	Q9NSC7	305
C2orf76	DRD5	P21918	305
C2orf76	STEAP3	Q658P3	277
C2orf76	NSFL1C	Q9UNZ2	220
C2orf76	CYP2A6	P00190	204

IntAct

4 interactions, top by confidence:

A	B	Type	Score
C2orf76	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
C2orf76	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): C2orf76 (Affinity Capture-RNA), C2orf76 (Two-hybrid), C2orf76 (Co-fractionation), ZADH2 (Co-fractionation), RBP7 (Co-fractionation)

ESM2 similar proteins: A7WLH8, G0SEV9, O57686, O80840, O94650, P18669, P25113, P42678, P55853, P63165, P63166, P91302, Q28BL6, Q2EF74, Q3KRA6, Q3SZ62, Q3T0Z3, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5RFB8, Q5VQ78, Q5ZLN1, Q6BUP7, Q6CU12, Q6DEP7, Q6EGX7, Q6FIX7, Q6GML7, Q6H8D5, Q6H8D6, Q6Q546, Q6Z8K4, Q756X3, Q791B0, Q7SXF2, Q7SZR5, Q8L828, Q8QGH2

Diamond homologs: A4IGN3, O14037, Q32KX9, Q3KRA6, Q54R16, Q5RBS7, Q66IB8, Q6DJH5, Q9CRW3, P36154

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

18 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1486 predictions. Top by Δscore:

Variant	Effect	Δscore
2:119302545:CTGG:C	acceptor_gain	1.0000
2:119311615:T:TA	donor_gain	1.0000
2:119311704:C:CC	acceptor_gain	1.0000
2:119339821:TCATA:T	donor_loss	1.0000
2:119339826:CCTTG:C	donor_gain	1.0000
2:119339846:AAATT:A	donor_gain	1.0000
2:119339850:T:A	donor_gain	1.0000
2:119302546:TGG:T	acceptor_gain	0.9900
2:119302549:C:CC	acceptor_gain	0.9900
2:119311699:TTTGT:T	acceptor_gain	0.9900
2:119311700:TTGT:T	acceptor_gain	0.9900
2:119311701:TGT:T	acceptor_gain	0.9900
2:119311702:GT:G	acceptor_gain	0.9900
2:119311702:GTCT:G	acceptor_loss	0.9900
2:119311703:TCTAA:T	acceptor_loss	0.9900
2:119311704:C:CA	acceptor_loss	0.9900
2:119311705:T:C	acceptor_loss	0.9900
2:119339850:T:TA	donor_loss	0.9900
2:119339968:ATTCC:A	acceptor_loss	0.9900
2:119339969:TTC:T	acceptor_gain	0.9900
2:119339969:TTCC:T	acceptor_loss	0.9900
2:119339972:C:CA	acceptor_loss	0.9900
2:119339973:T:G	acceptor_loss	0.9900
2:119366490:TTCC:T	donor_gain	0.9900
2:119366590:A:AC	donor_gain	0.9900
2:119366591:C:CC	donor_gain	0.9900
2:119366610:T:TA	donor_gain	0.9900
2:119302548:GCT:G	acceptor_loss	0.9800
2:119302549:CT:C	acceptor_loss	0.9800
2:119302550:T:A	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000068537 (2:119368613 T>C), RS1000083228 (2:119281840 A>T), RS1000106969 (2:119345857 T>C), RS1000137973 (2:119345691 G>A), RS1000156190 (2:119307633 C>G), RS1000164406 (2:119339185 C>T), RS1000201298 (2:119366117 C>A), RS1000231567 (2:119320879 T>C), RS1000248965 (2:119313703 C>G,T), RS1000353328 (2:119326600 A>G), RS1000422161 (2:119333003 G>C), RS1000438152 (2:119351478 C>T), RS1000502910 (2:119364469 T>C), RS1000559093 (2:119301393 A>T), RS1000581516 (2:119312251 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Estradiol	decreases expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Dihydrotestosterone	increases expression	1
Thimerosal	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.